Alexander R. Opotowsky

Arrhythmia Burden in Adults With Surgically Repaired Tetralogy of Fallot A Multi-Institutional Study

Background— The arrhythmia burden in tetralogy of Fallot, types of arrhythmias encountered, and risk profile may change as the population ages. Methods and Results— The Alliance for Adult Research in Congenital Cardiology (AARCC) conducted a multicenter cross-sectional study to quantify the arrhythmia burden in tetralogy of Fallot, to characterize age-related trends, and to identify associated factors. A total of 556 patients, 54.0% female, 36.8±12.0 years of age were recruited from 11 centers. Overall, 43.3% had a sustained arrhythmia or arrhythmia intervention. Prevalence of atrial tachyarrhythmias was 20.1%. Factors associated with intraatrial reentrant tachycardia in multivariable analyses were right atrial enlargement (odds ratio [OR], 6.2; 95% confidence interval [CI], 2.8 to 13.6), hypertension (OR, 2.3; 95% CI, 1.1 to 4.6), and number of cardiac surgeries (OR, 1.4; 95% CI, 1.2 to 1.6). Older age (OR, 1.09 per year; 95% CI, 1.05 to 1.12), lower left ventricular ejection fraction (OR, 0.93 per unit; 95% CI, 0.89 to 0.96), left atrial dilation (OR, 3.2; 95% CI, 1.5 to 6.8), and number of cardiac surgeries (OR, 1.5; 95% CI, 1.2 to 1.9) were jointly associated with atrial fibrillation. Ventricular arrhythmias were prevalent in 14.6% and jointly associated with number of cardiac surgeries (OR, 1.3; 95% CI, 1.1 to 1.6), QRS duration (OR, 1.02 per 1 ms; 95% CI, 1.01 to 1.03), and left ventricular diastolic dysfunction (OR, 3.3; 95% CI, 1.5 to 7.1). Prevalence of atrial fibrillation and ventricular arrhythmias markedly increased after 45 years of age. Conclusions— The arrhythmia burden in adults with tetralogy of Fallot is considerable, with various subtypes characterized by different profiles. Atrial fibrillation and ventricular arrhythmias appear to be influenced more by left- than right-sided heart disease.

Trends in hospitalizations for adults with congenital heart disease in the U.S.

OBJECTIVES The purpose of this study was to better define the epidemiology of hospitalizations for adults with congenital heart disease (ACHD) in the U.S. BACKGROUND There is a growing population of ACHD as the result of advances in pediatric care and diagnostic testing. METHODS We used nationally representative data from the 1998 to 2005 Nationwide Inpatient Sample to identify patients > or =18 years of age admitted to an acute care hospital with an International Classification of Diseases-9th Revision code designating a CHD diagnosis. National estimates of hospitalizations and total hospital charges by year were calculated. RESULTS The number of ACHD hospitalizations increased 101.9% from 35,992 +/- 2,645 in 1998 to 72,656 +/- 5,258 in 2005. During this period, the annual number of admissions grew for both simple (19,448 +/- 1,614 to 44,707 +/- 3,644) and complex (12,507 +/- 1,172 to 19,973 +/- 1,624) diagnoses. The percentage of admissions originating in the emergency department (41.7 +/- 0.8%) or involving cardiac surgery (17.7 +/- 0.7%) remained stable during the study period. The average patient age (52.3 +/- 0.8 years to 53.8 +/- 0.6 years, p < 0.0001) and proportion of patients with > or =2 medical comorbidities (23.3 +/- 0.9% to 33.0 +/- 0.7%, p < 0.0001) increased. Mean hospital charges per hospitalization increased 127% from 19,186 +/- 803 to 43,496 +/- 2,166 US dollars, and the estimated total national charges for these hospitalizations increased 357% from 691 million US dollars in 1998 to 3.16 billion US dollars in 2005 (in inflation-adjusted 2005 dollars). CONCLUSIONS The number of hospital admissions for ACHD in the U.S. more than doubled between 1998 and 2005. Hospital charges attributable to these admissions have grown even more dramatically.

Prevalence of Left Ventricular Systolic Dysfunction in Adults With Repaired Tetralogy of Fallot

Left ventricular (LV) systolic dysfunction has been observed in patients with repaired tetralogy of Fallot (TOF), although its clinical associations are unknown. Adults with repaired TOF were identified from 11 adult congenital heart disease centers. Clinical history was reviewed. Patients with pulmonary atresia were excluded. Echocardiograms were reanalyzed to estimate LV ejection fraction. LV function was defined as normal (LV ejection fraction ≥ 55%) or mildly (45% to 54%), moderately (35% to 44%), or severely (< 35%) decreased. Right ventricular (RV) and LV dimensions and Doppler parameters were remeasured. Function of all valves was qualitatively scored. Of 511 patients studied, LV systolic dysfunction was present in 107 (20.9%, 95% confidence interval 17.4 to 24.5). Specifically, 74 (14.4%) had mildly decreased and 33 (6.3%) had moderately to severely decreased systolic function. Presence of moderate to severe LV dysfunction was associated with male gender, LV enlargement, duration of shunt before repair, history of arrhythmia, QRS duration, implanted cardioverter-defibrillator, and moderate to severe RV dysfunction. Severity or duration of pulmonary regurgitation was not different. In conclusion, LV systolic dysfunction was found in 21% of adult patients with TOF and was associated with shunt duration, RV dysfunction, and arrhythmia.

Prevalence and predictors of gaps in care among adult congenital heart disease patients: HEART-ACHD (The Health, Education, and Access Research Trial)

OBJECTIVES The goal of this project was to quantify the prevalence of gaps in cardiology care, identify predictors of gaps, and assess barriers to care among adult congenital heart disease (adult CHD) patients. BACKGROUND Adult CHD patients risk interruptions in care that are associated with undesired outcomes. METHODS Patients (18 years of age and older) with their first presentation to an adult CHD clinic completed a survey regarding gaps in, and barriers to, care. RESULTS Among 12 adult CHD centers, 922 subjects (54% female) were recruited. A >3-year gap in cardiology care was identified in 42%, with 8% having gaps longer than a decade. Mean age at the first gap was 19.9 years. The majority of respondents had more than high school education and knew their heart condition. The most common reasons for gaps included feeling well, being unaware that follow-up was required, and complete absence from medical care. Disease complexity was predictive of a gap in care with 59% of mild, 42% of moderate, and 26% of severe disease subjects reporting gaps (p < 0.0001). Clinic location significantly predicted gaps (p < 0.0001), whereas sex, race, and education level did not. Common reasons for returning to care were new symptoms, referral from provider, and desire to prevent problems. CONCLUSIONS Adult CHD patients have gaps in cardiology care; the first lapse commonly occurred at age ∼19 years, a time when transition to adult services is contemplated. Gaps were more common among subjects with mild and moderate diagnoses and at particular locations. These results provide a framework for developing strategies to decrease gaps and address barriers to care in the adult CHD population.

Transcatheter Potts shunt creation in patients with severe pulmonary arterial hypertension: Initial clinical experience

BACKGROUND Patients with severe pulmonary arterial hypertension (PAH) face significant morbidity and death as a consequence of progressive right heart failure. Surgical shunt placement between the left PA and descending aorta (Potts shunt) appears promising for PAH palliation in children; however, surgical mortality is likely to be unacceptably high in adults with PAH. METHODS We describe a technique for transcatheter Potts shunt (TPS) creation by fluoroscopically guided retrograde needle perforation of the descending aorta at the site of apposition to the left PA to create a tract for deployment of a covered stent between these vessels. This covered stent-anchored by the vessel walls and surrounding tissue-serves as the shunt. RESULTS TPS creation was considered in 7 patients and performed in 4. The procedure was technically successful in 3 patients; 1 patient died during the procedure as a result of uncontrolled hemothorax. One acute survivor, critically ill at the time of TPS creation, later died of comorbidities. The 2 mid-term survivors (follow-up of 10 and 4 months) are well at home, with symptomatic improvement and no late complications. The 3 candidate patients in whom the procedure was not performed died within 1 month of consideration, underscoring the tenuous nature of this population. CONCLUSIONS TPS creation is feasible and may offer symptomatic relief to select patients with refractory PAH. Further study of this innovative approach is warranted.

Application of Appropriateness Criteria in Outpatient Transthoracic Echocardiography

BACKGROUND Appropriateness criteria were applied to outpatient transthoracic echocardiographic (TTE) studies. METHODS Indications were rated as appropriate, inappropriate, or unclassifiable, considering provider-stated indications, previous TTE studies, symptom changes, and patient-stated indications. Clinically important new or unexpected findings were recorded. RESULTS Of 368 TTE studies, 206 (56%) were appropriate, 31 (8%) were inappropriate, and 131 (35%) were unclassifiable. Appropriateness was not correlated with patient or provider demographics. In 288 cases with prior TTE studies, there were 92 (32%) important new findings and 63 (22%) unexpected findings, of which 20% were from inappropriately ordered and 31% from unclassifiable TTE studies. Appropriateness was not associated with new (odds ratio, 1.23; 95% confidence interval, 0.48-3.18) or unexpected (odds ratio, 1.15; 95% confidence interval, 0.38-3.52) findings. Provider type and level of training were not correlated with new or unexpected findings. CONCLUSIONS Many indications for TTE studies were unclassifiable. A high percentage of inappropriately ordered TTE studies yielded important information. Care must be taken in judging the value of TTE studies solely on the basis of appropriateness criteria.

Maternal cardiovascular events during childbirth among women with congenital heart disease

Objectives To define the epidemiology of adverse cardiovascular events among women with congenital heart disease (CHD) hospitalised for childbirth in the USA. Design and setting The 1998–2007 Nationwide Inpatient Sample, an administrative dataset representative of overall US hospital admissions, was used to identify hospitalisations for delivery. Main outcome measures Logistic regression was used to estimate ORs for cardiovascular outcomes (arrhythmia, heart failure, cerebrovascular accident, embolism, death or a combined outcome) for women with and without CHD. Covariates included age, number of medical comorbidites, pulmonary hypertension, hospital teaching status, insurance status and method of delivery. Results Annual deliveries for women with CHD increased 34.9% from 1998 to 2007 compared with an increase of 21.3% in the general population. Women with CHD were more likely to sustain a cardiovascular event (4042/100 000 vs 278/100 000 deliveries, univariate OR 15.1, 95% CI 13.1 to 17.4, multivariable OR 8.4, 95% CI 7.0 to 10.0). Arrhythmia, the most common cardiovascular event, was more frequent among women with CHD (2637/100 000 vs 210/100 000, univariate OR 12.9, 95% CI 10.9 to 15.3, multivariable OR 8.3, 95% CI 6.7 to 10.1). Death occurred in 150/100 000 patients with CHD compared with 8.2/100 000 patients without CHD (multivariable OR 6.7, 95% CI 2.9 to 15.4). Complex CHD was associated with greater odds of having an adverse cardiovascular event than simple CHD (8158/100 000 vs 3166/100 000, multivariable OR 2.0, 95% CI 1.4 to 3.0). Conclusions Maternal CHD is associated with a markedly increased risk of adverse cardiovascular events and death during admission for delivery.

Trends in the Use of Percutaneous Closure of Patent Foramen Ovale and Atrial Septal Defect in Adults, 1998-2004

of participants ( 10%) had a left ventricular ejection fraction less than 40%. The baseline prevalence of job strain exposure in our participants and in the general Quebec working population were comparable (18% vs 22%, respectively), indicating no tendency to overestimate job strain exposure in our participants. Hassan et al suggest that a possible explanation of our results might be misclassification due to the selection of sicker patients whose subsequent perception led to self-report into the chronic strain group. As we noted, selection bias is unlikely. It is also unlikely that sickness and perception explain the observed association because the data used to classify patients’ exposure to chronic job strain were collected before patients knew about their relevant recurrent coronary heart disease event. (As shown in Figure 2 and Table 3, the effect is observed after the 2-year interview.) In addition, models were adjusted for psychological distress (depression symptoms, anxiety, cognitive disturbances, and anger) and personality factors (Table 4) using validated scales. Finally, all analyses were preplanned.

Genetic and hypoxic alterations of the microRNA‐210‐ISCU1/2 axis promote iron–sulfur deficiency and pulmonary hypertension

Iron–sulfur (Fe‐S) clusters are essential for mitochondrial metabolism, but their regulation in pulmonary hypertension (PH) remains enigmatic. We demonstrate that alterations of the miR‐210‐ISCU1/2 axis cause Fe‐S deficiencies in vivo and promote PH. In pulmonary vascular cells and particularly endothelium, hypoxic induction of miR‐210 and repression of the miR‐210 targets ISCU1/2 down‐regulated Fe‐S levels. In mouse and human vascular and endothelial tissue affected by PH, miR‐210 was elevated accompanied by decreased ISCU1/2 and Fe‐S integrity. In mice, miR‐210 repressed ISCU1/2 and promoted PH. Mice deficient in miR‐210, via genetic/pharmacologic means or via an endothelial‐specific manner, displayed increased ISCU1/2 and were resistant to Fe‐S‐dependent pathophenotypes and PH. Similar to hypoxia or miR‐210 overexpression, ISCU1/2 knockdown also promoted PH. Finally, cardiopulmonary exercise testing of a woman with homozygous ISCU mutations revealed exercise‐induced pulmonary vascular dysfunction. Thus, driven by acquired (hypoxia) or genetic causes, the miR‐210‐ISCU1/2 regulatory axis is a pathogenic lynchpin causing Fe‐S deficiency and PH. These findings carry broad translational implications for defining the metabolic origins of PH and potentially other metabolic diseases sharing similar underpinnings.

Aortic Root Dilatation in Adults with Surgically Repaired Tetralogy of Fallot A Multicenter Cross-Sectional Study

Background— Although aortic root pathology has been described in patients with tetralogy of Fallot, the scope of the problem remains poorly defined. We sought to determine the prevalence and predictors of aortic root dilatation in adults with repaired tetralogy of Fallot. Methods and Results— A multicenter cross-sectional study was conducted with standardized reassessment of echocardiographic parameters in 474 adults (≥18 years) with surgically repaired tetralogy of Fallot or pulmonary atresia with ventricular septal defect. The aortic root was measured in a parasternal long-axis view, in diastole, at the level of the sinus of Valsalva. Prevalence and predictors of an absolute diameter ≥40 mm and of an observed-to-expected ratio >1.5 were assessed. The aortic root dimension was ≥40 mm in 28.9% (95% confidence interval, 26.9%–30.9%). In multivariate analyses, the only independently associated factor was male sex (odds ratio, 4.48; 95% confidence interval, 1.55–12.89; P=0.006). The prevalence of an observed-to-expected aortic root dimension ratio >1.5 was 6.6% (95% confidence interval, 5.3%–7.9%). It was associated with pulmonary atresia and moderate or severe aortic regurgitation in univariate analyses, but no independent predictor was identified. The side of the aortic arch was not associated with aortic root dimension. The prevalence of moderate or severe aortic regurgitation was 3.5% (95% confidence interval, 2.7%–4.2%). Conclusions— Although nearly one third of adults with repaired tetralogy of Fallot have an aortic root diameter ≥40 mm, the prevalence of a dilated aortic root, when defined by an indexed ratio of observed-to-expected values, is low. Similarly, moderate or severe aortic regurgitation is uncommon.